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首页> 外文期刊>Infection and immunity >Role for Fimbriae and Lysine-Specific Cysteine Proteinase Gingipain K in Expression of Interleukin-8 and Monocyte Chemoattractant Protein in Porphyromonas gingivalis-Infected Endothelial Cells
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Role for Fimbriae and Lysine-Specific Cysteine Proteinase Gingipain K in Expression of Interleukin-8 and Monocyte Chemoattractant Protein in Porphyromonas gingivalis-Infected Endothelial Cells

机译：菌毛和赖氨酸特异性半胱氨酸蛋白酶Gingipain K在感染牙龈卟啉单胞菌的内皮细胞中白介素8和单核细胞趋化蛋白的表达中的作用。

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Recent cross-sectional and prospective epidemiological studies have demonstrated an association between periodontal disease and atherosclerosis and human coronary heart disease. Previously, we have established that the periodontal pathogen Porphyromonas gingivalis is capable of invading aortic, heart, and human umbilical vein endothelial cells (HUVEC). Since atherosclerosis is a chronic inflammatory response initiated at the vascular wall, interactions of P. gingivalis with endothelial cells and the subsequent host cell response to infection may be important in the pathogenesis of atherosclerosis. In this study we examined the consequences of P. gingivalis infection of HUVEC on the expression of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1). HUVEC were found to constitutively produce low levels of IL-8 and MCP-1. The addition of P. gingivalis fimbrillin-specific peptides, lipopolysaccharides (LPS), or heat-killed whole cell preparations to HUVEC stimulated modest IL-8 and MCP-1 responses. In contrast, coculture of HUVEC with live P. gingivalis strain A7436, 33277, or 381 abolished the IL-8 and MCP-1 responses. Inhibition of IL-8 and MCP-1 production was not dependent on bacterial adherence since similar results were obtained with the nonadherent P. gingivalis fimA mutant DPG3 or when P. gingivalis was preincubated with fimbrillin peptide antisera prior to the addition to HUVEC. Furthermore, treatment of P. gingivalis-infected HUVEC with cytochalsin D, which prevented P. gingivalis invasion, also abolished the constitutive IL-8 and MCP-1 responses. Treatment of HUVEC with E. coli LPS stimulated robust IL-8 and MCP-1 responses that were abolished when stimulated cells were cocultured with live P. gingivalis. Analysis of P. gingivalis-infected HUVEC cultures by an RNase protection assay revealed an increase in the IL-8 transcript relative to uninfected HUVEC. Pretreatment of P. gingivalis with protease inhibitors prior to the addition to HUVEC prevented the inhibition of IL-8 and MCP-1 production in P. gingivalis-infected HUVEC, indicating that the inhibition was proteolytically mediated. Coculture of HUVEC with a P. gingivalis mutant deficient in lysine-specific cysteine proteinase (gingipain K [Kgp]) resulted in an increase in both IL-8 transcription and protein expression relative to that observed in HUVEC cocultured with the P. gingivalis wild-type strain. These results indicate that P. gingivalis can temporally modulate the chemokine response in endothelial cells through both fimbriae and gingipain-mediated mechanisms.
机译：最近的横断面和前瞻性流行病学研究表明，牙周疾病与动脉粥样硬化和人类冠心病之间存在关联。以前，我们已经确定牙周病原体 Porphyromonas gingivalis 能够侵入主动脉，心脏和人脐静脉内皮细胞（HUVEC）。由于动脉粥样硬化是在血管壁处引发的慢性炎症反应，因此 P的相互作用。牙龈内皮细胞和随后的宿主细胞对感染的反应可能在动脉粥样硬化的发病机理中起重要作用。在这项研究中，我们检查了 P的后果。 HUVEC牙龈感染对趋化因子白细胞介素8（IL-8）和单核细胞趋化蛋白1（MCP-1）表达的影响。发现HUVEC组成型产生低水平的IL-8和MCP-1。 P的添加。对HUVEC刺激的中度龈炎球菌特异性肽，脂多糖（LPS）或热灭活的全细胞制剂，可引起适度的IL-8和MCP-1反应。相反，HUVEC与活的 P共培养。牙龈炎菌株A7436、33277或381消除了IL-8和MCP-1反应。 IL-8和MCP-1产生的抑制不取决于细菌的粘附，因为使用非粘附的 P可获得相似的结果。 gingivalis fimA 突变DPG3或 P时。在加入HUVEC之前，先将其与抗纤毛蛋白血清一起预孵育。此外，治疗 P。牙龈D感染了龈牙龈炎感染的HUVEC，可预防 P。牙龈的侵袭，也消除了IL-8和MCP-1的本构反应。用 E治疗HUVEC。 LPS刺激了强烈的IL-8和MCP-1反应，而刺激的细胞与活的P共培养时却被消除了。牙龈炎。对 P的分析。核糖核酸酶保护法检测牙龈感染的HUVEC培养物，与未感染的HUVEC相比，IL-8转录本增加。 P的预处理。在加入HUVEC之前，添加蛋白酶抑制剂的牙龈炎可阻止 P中IL-8和MCP-1的产生。牙龈感染 HUVEC，表明该抑制作用是由蛋白水解介导的。 HUVEC与 P的共培养。缺乏赖氨酸特异性半胱氨酸蛋白酶（gingipain K [Kgp]）的牙龈突变导致IL-8转录和蛋白质表达均相对于与 P共培养的HUVEC有所增加。牙龈野生菌株。这些结果表明 P。牙龈炎可以通过菌毛和牙龈蛋白酶介导的机制在时间上调节内皮细胞的趋化因子反应。

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